Digital chemical analysis apparatus

ABSTRACT

The disclosure describes an improved system for evaluating rates of reactions and end point determinations that take place within a plurality of individaul secimens. The system includes a cuvette for holding each of the specimens in an individual compartment. Analyzing apparatus is used to generate and sequentially transmit a beam of radiant energy through each of the specimens. The analysis apparatus also produces an analysis signal having a value proportional to a property of a particular specimen each time the beam passes through that specimen. Cycling apparatus causes the beam to sequentially and separately pass through each of the specimens during multiple cycles of operation. During the first cycle of operation, a first set of analysis signals having a first set of values corresponding to the specimens is created. Likewise, during a second cycle of operation, a second set of analysis signals having a second set of values corresponding to the specimens is created. In order to determine the rate at which the reactions take place within each of the specimens, a memory is used to store at least the first set of values. Then, during the second cycle of operation, a processing circuit compares the values of the first and second sets of values which correspond to the same specimen. In this way, the rate of reaction of each specimen is automatically determined. By a similar technique, values can be created and compared in seconds in order to determine rates of reactions that proceed rapidly. In order to analyze end joint determinations, one of the specimens comprises a known concentration of a substance, and other specimens contain unknown concentrations of the substance. The value corresponding to the known concentration is stored in the memory, and other values correspndingly to the unknown concentration are compared with the value stored in the memory. Improved components of the system such as a cuvette, a specimen dispenser, and an analyzing apparatus are also disclosed in the specification. The analyzing apparatus preferably comprises apparatus for instantaneously determining the concentration of a predetermined substance that absorbs radiant energy within a predetermined band of wavelengths in the presence of other interfering substances that also absorb radiant energy in the region of the predetermined band. The determination is made by generating multiple wavelengths of radiant energy. The radiant energy is then sequentially transmitted in a single path through the substances, and the transmission is periodically interrupted by means which prevent the transmission of any radiation. The intensities of the radiant energy transmitted through the substances at the various wavelengths are then compared by electronic apparatus.

United States Patent 119i Liston v 14 1 July 24, 1973 [5 1 mcrrsr. CHEMICAL ANALYSIS APPARATUS [75] Inventor: Max D. Liston, Irvine, Calif.

[73] Assignee: Abbott Laboratories, North Chicago,

Ill. 3 I

[22] Filed: Apr. 12, 1971 [2l] Appl. No.: 133,081

Related 0.8. Application Data [63] Continuation-impart of Ser. No. 854,647, Sept. 2,

I969, Pat. No. 3,664,744.

[56] .Refere nees Cited UNITED STATES PATENTS 3,542,515 11/1970 sc61t.;.,.;...,;. .;..'356/95 3,344,702 10/1967 Wood 61:11. .356/179 3,528,749 9/1970 Bowker... 356/223 3,567,393 3/1971 Welch 356 186 2,879,141 3 1959 Slteggs 356/246 3,089,382 5/1963 Hechl et al. 356/96 3,247,758 4/1966 'Iumer..."... 356/101 3,266,298 8/1966 Whitehead 6161.. 73/53 3,471,242 10/1969 Nichols 356/189 3,56l,875 2/1971 Ried, Jr. et al." 356/205 .3,526,l25 Gilford etal. 73/53 I Primary Excmirter konald lirWibert'l- Assistant Examiner-5], P. McGraw' 3 1 Attorriey'-.Molinare, Allegretti, Newitt & Witcoff 57 i :Ans'mh'cr; v v The disclosure describes an impr oved'system for evaluatingrates of reactions and end point determinations I that take place within applurality of individaul seeimens. The systemincludesa cuvettejfor holding each of the specimens in'an individual compartment; Anaspecimens; [The analysis apparatus also produces an analysis signal having a value proportional toa property of a particular specimen each time the beam passes through that specimen. Cycling apparatus causes the beam to sequentially and separately pass through each of the specimens during multiple cycles of operation. During the first cycle of operation, a first set of analysis signals having a first set of values corresponding to the specimens is created. Likewise, during a second cycle of operation, a second set-of analysis signals having a second set of values corresponding to'the specimens is created.

In order to determine the rate at which the reactions take place within each of the specimens, a memory is used to storeat least the first set of values. Then, during the second cycle of operation, a. processing circuit compares the values of the first and second sets of values which correspond to the'same specimen. In this way, the rate of reaction of each specimen is automatically determined. By a similar technique,

values can be created and compared in secondsin order to determine rates of reactions that proceed rapidly. 1

In order to analyze end joint determinations, one of the specimens comprises a known concentration of a substance, and otherv specimens contain unknown concentrations of the substance. The value corresponding to the known concentration is stored in the memory, and other values correspndingly to the unknown concentration are "compared with the value stored in the memory. p Improved components of the system such as a cuvette', a specimen dispenser, and'an. analyzing apparatus are also disclosedin the specification.

The analyzing apparatus preferably comprises apparatus for instantaneously determining the concentration of a predetermined substance that by generating multiple wavelengths of 'radiantenergy.

The radiant energy is, then sequentially transmitted in a single path through the "substances, and. the transmission is periodically interrupted bymeans which prevent the transmission of any radiation; The intensities of the radiant energy transmitted .through the substances at the various wavelengths are then compared by electronic apparatus.

- 15 Claims, 4 6ibrawing'l igures 5 United States Patent '[191 [111 3,748,044

Liston July 24, 1973 PAIENIED 3.748.044

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1. A system for analyzing reactions which take place within a plurality of individual specimens comprising: curvette means for holding each of the specimens in an individual compartment; analyzing means for generating and transmitting a beam of radiant energy through the specimens and for producing an analysis signal having a value proportional to a property of a predetermined specimen each time the beam passes through the predetermined specimen; cycling means for causing the beam to sequentially pass through predetermined ones of the specimens during predetermined cycles of operation to produce a set of analysis signals, each said analysis signal having a value corresponding to one of the predetermined specimens; converter means for converting each analysis signal into a corresponding digital signal representing a digital number; address means for generating an identity code that uniquely identifies each of the predetermined specimens; memory means for storing at least one of the digital numbers at an address corresponding to a particular one of the predetermined specimens; and electronic processing means for enabling the cycling means and for comparing the one or more digital numbers stored in the memory means with additional digital numbers created by the analyzing means and cycling means in order to analyze the reaction of the predetermined specimens.
 2. A system, as claimed in claim 1, wherein the memory means comprises semiconductor means for storing a plurality of first data bits at an address, for reading out the plurality of first data bits, and for storing at said address a plurality of second data bits different from the first data bits in response to electrical control signals.
 3. A system, as claimed in claim 1, wherein said converter means comprises: pulse geNerator means for producing generated pulses at a predetermined rate; counting means for counting said generating pulses; gate means for transmitting the generated pulses to the counting means in a number proportional to the value of an analysis signal and; means for selectively enabling the counting means to count in either one of two directions, whereby reactions resulting in either greater or lesser radiant energy absorption by the specimen may be analyzed.
 4. A system, as claimed in claim 1, wherein the processing means comprises: a source of signals; clock means for dividing the signals and for producing a plurality of start pulses at predetermined time intervals; gate means for producing control pulses in response to a start pulse; means for counting the cycles of operation of the cycling means and for disabling certain of the gate means during predetermined and programmable cycles of operation of the cycling means; and means for transmitting predetermined ones of the start pulses to the gate means, whereby the cycling means is operated at a predetermined rate.
 5. A system for analyzing a first specimen and a second specimen comprising: curvette means for holding the first and second specimens individually; analyzing means for generating an analyzing beam adapted to pass through the first and second specimens to produce a transmitted beam and for converting each such transmitted beam into an electrical analysis signal having a value proportional to a property of the corresponding first or second specimen; cycling means for moving the cuvette means and the analyzing means into a first position in which the analyzing beam is directed through the first specimen and for moving the cuvette means and the analyzing means into a second position in which the analyzing beam is directed through the second specimen during each cycle of operation; first processing means for causing the cycling means to complete at least a first cycle of operation, whereby a first analysis signal having a first value is created at the first position and a second analysis signal having a second value is created at the second position; converter means for converting the first analysis signal into a corresponding first digital signal representing a first digital number and for converting the second analysis signal into a corresponding second digital signal representing a second digital number; memory means for storing at least the first digital number; and second electronic processing means for reading the first digial number from memory and for comparing at least the first and second digital numbers, whereby at least the first and second specimens are compared.
 6. A system, as claimed in claim 5, wherein said converter means comprises: pulse generator means for producing generating pulses at a predetermined rate; counting means for counting said generated pulses; gate means for transmitting the generated pulses to the counting means in a number proportional to the value of an analysis signal and; means for selectively enabling the counting means to count in either one of two directions, whereby reactions resulting in either greater or lesser radiant energy absorption by the specimen may be analyzed.
 7. A system, as claimed in claim 6, wherein the first and second processing means comprise: first means for energizing the cycling means whereby the cuvette means and analyzing means are moved with respect to each other so that the analyzing beam is trans-mitted through the first specimen; second means for energizing the analyzing means to produce the first digital signal corresponding to the first specimen and for entering the first digital signal representing the first digital number in the counting means; third means for transmitting the first digital number entered in the counting means to the memory means; fourth means for storing the first digital number in the memory Means; fifth means for energizing the cycling means whereby the cuvette means and the analyzing means are moved with respect to each other so that the analyzing beam is trans-mitted through the second specimen; sixth means for entering in the counting means the first digital number; and seventh means for energizing the analyzing means to produce the second digital signal representing the second digital number corresponding to the second specimen and for subtracting the second digital number from the first digital number entered in the counting means to produce a remainder digital number.
 8. A system for analyzing a first specimen and a second specimen comprising: cuvette means for holding the first and second specimens individually; analyzing means for generating an analyzing beam adapted to pass through the first and second specimens to produce a transmitted beam and for converting each such transmitted beam into an electrical analysis signal having a value proportional to a property of the corresponding first or second specimen; cycling means for moving the cuvette means and the analyzing means into a first position in which the analyzing beam is directed through the first specimen and for moving the cuvette means and the analyzing means into a second position in which the analyzing beam is directed through the second specimen during each cycle of operation; first processing means for causing the cycling means to complete a first cycle of operation, whereby a first analysis signal having a first value is created at the first position and a second analysis signal having a second value is created at the second position and for causing the cycling means to complete a second cycle of operation, whereby a third analysis signal having a third value is created at the first position in a predetermined time period after the first analysis signal and a fourth value is created at the second position in said predetermined time period after the second analysis signal; converter means for converting the first analysis signal into a corresponding first digital signal representing a first digital number, for converting the second analysis signal into a corresponding second digital signal representing a second digital number, for converting the third analysis signal into a corresponding third digital signal representing a third digital number and for converting the fourth analysis signal into a corresponding fourth digital signal representing a fourth digital number; memory means for storing the first and second digital numbers during the first cycle of operation; and second electronic processing means operative during the second cycle of operation for comparing the first and third digital numbers and for comparing the second and fourth digital numbers, whereby the rates of reaction of the first and second specimens are determined.
 9. A system, as claimed in claim 8, wherein said converter means comprises: pulse generator means for producing generated pulses at a predetermined rate; counting means for counting said generated pulses; gate means for transmitting the generated pulses to the counting means in a number proportional to the value of an analysis signal; and means for selectively enabling the counting means to count in either one of two directions, whereby reactions resulting in either greater or lesser radiant energy absorp-tion by the specimen may be analyzed.
 10. A system, as claimed in claim 9, wherein said first and second processing means comprise: first means for energizing the cycling means whereby the cuvette means and the analyzing means are moved with respect to each other so that the beam is transmitted through a predetermined one of the specimens; second means for entering in the counting means the stored digital number stored in the memory means which corresponds to the predetermined specimen; third means for energizing the analyzing means to produce a current digital signal Representing a current digital number corresponding to the predeter-mined specimen and for subtracting the current digital number from the stored digital number to produce a remainder digital number; fourth means for energizing the display means, whereby the remainder digital number is displayed; fifth means for energizing the analyzing means to produce in the counting means a storable digital signal representing a storable digital number corresponding to the predetermined specimen; sixth means for transferring the storable digital number entered in the counting means to the predetermined memory means; and seventh means for energizing the cycling means whereby the cuvette means and the analyzing means are moved with respect to each other so that the beam is transmitted through another one of the specimens.
 11. A system, as claimed in claim 10, wherein said second means comprises means for causing said counting means to count in a first direction and said third means comprises means for causing said counting means to count in a direction opposite said first direction.
 12. A system, for analyzing a specimen comprising: cuvette means for holding the specimen; analyzing means for generating an analyzing beam adapted to pass through the specimen to produce a transmitted beam and for converting the transmitted beam into an electrical analysis signal having a value that changes in proportion to a property of the specimen; converter means for converting each analysis signal into a corresponding digital signal representing a digital number; positioning means for supporting the cuvette means and the analyzing means in a position in which the analyzing beam is directed through the specimen; memory means for storing the value of the analysis signal; first processing means for cyclically storing in the memory means the digital numbers corresponding to the values of the analysis signal at points of time displaced by a predetermined time period; and second electronic processing means for comparing the digital numbers cyclically stored in the memory means, whereby the rate of reaction of the specimen is determined.
 13. A system, as claimed in claim 12, wherein said converter means comprises: pulse generator means for producing generated pulses at a predetermined rate; digital counting means for counting said generated pulses; gate means for transmitting the generated pulses to the counting means in a number proportional to the value of an analysis signal; and means for selectively enabling the counting means to count in either one of two directions, whereby reactions resulting in either greater or lesser radiant energy absorp-tion by the specimen may be analyzed.
 14. A system, as claimed in claim 13, wherein the first and second processing means comprise: first means for entering in the counting means a stored digital number stored in the memory means which coresponds to the specimen; second means for energizing the analyzing means to produce a current digital signal representing a current digital number corresponding to the specimen and for subtracting the current digital number from the stored digital number entered in the counting means to produce a remainder digital number; third means for energizing the analyzing means to produce in the counting means a storable digital signal representing a storable digital number corresponding to the specimen; and fourth means for transferring the storable digital number entered in the counting means to the memory means, so that the storable digital number may be subsequently compared with another digital number derived from another analysis signal whereby the rate of reaction occurring within the specimen is determined.
 15. A system, as claimed in claim 14, wherein the first processing means comprises clock means for producing clock pulses displaced in time by a predetermined time period so that the values cyclically stored in The memory means are compared at points of time displaced by the predetermined time period. 